International patent application no. WO99/21855 (SmithKline Beecham plc and SmithKline Beecham Corporation) describes pleuromutilin derivatives of general formula (A) or (B):
in which:each of n and m is independently 0, 1 or 2;X is selected from —O—, —S—, —S(O)—, —SO2—, —CO.O—, —NH—, —CONH—, —NHCONH— and a bond;R1 is vinyl or ethyl;R2 is a non-aromatic monocyclic or bicyclic group containing one or two basic nitrogen atoms and attached through a ring carbon atom;R3 is H or OH; orthe moiety R2(CH2)mX(CH2)nCH2COO at position 14 of (IA) or (IB) is replaced by RaRbC═CHCOO in which one of Ra and Rb is hydrogen and the other is R2 or Ra and Rb together form R2, ora pharmaceutically acceptable salt thereof.
One of the compounds described in WO99/21855 is the compound of formula (C), mutilin 14-(exo-8-methyl-8-azabicyclo[3.2.1]oct-3-ylsulfanyl)-acetate:

Two processes for the preparation of this compound are described in Examples 50 and 58 of WO99/21855. In the first process, mutilin 14-methanesulfonyloxyacetate is added to endo-8-methyl-8-azabicyclo[3.2.1]octan-3-thiol in the presence of potassium t-butoxide in ethanol, to give the product in a yield of 17% based on the amount of pleuromutilin derived starting material, after purification. The thiol was prepared from the corresponding hydroxy compound via the corresponding thioacetate. In the second process, the methane sulfonate leaving group is located on the methyl-8-azabicyclo[3.2.1]octyl component which is added to 22-deoxy-22-sulfanylpleuromutilin in the presence of sodium methoxide, to give the product in a yield of 27% based on the amount of pleuromutilin derived starting material, after purification.